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Cancer Cell International
Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Primary research

B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer

Authors: Ling Wang, Chao Yang, Xin-bo Liu, Li Wang, Fu-biao Kang

Published in: Cancer Cell International | Issue 1/2018

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Abstract

Background

The expression of the immunoregulatory protein B7-H4 has been reported in many types of cancer, including breast cancer. However, its role in triple-negative breast cancer (TNBC), especially its correlation with patients’ prognosis and chemoresistance remains unclear.

Methods

The expression of B7-H4 in TNBC tissues and cell lines were measured with Real-Time PCR and western blotting. 65 cases of TNBC tissue samples and adjacent non-tumor tissue samples were analyzed by immunochemistry to demonstrate the correlation between the B7-H4 expression and clinicopathological characteristics. In vitro studies assessed mAb MIH43 alone and in combination with transfecting B7-H4 siRNA on the growth of chemosensitive and chemoresistant TNBC cell lines by CCK-8 and apoptotic enzyme-linked immunosorbent assay (ELISA).

Results

B7-H4 expression was detected positive in 59 of 65 (90.8%) different stage TNBC patients, especially in the samples of recurrence TNBC patients after receiving neoadjuvant chemotherapy treatment. Survival curves showed that patients with B7-H4 overexpression had significantly shorter survival and recurrence time than those with low B7-H4 expression (p < 0.005). Univariate and multivariate COX regression analysis demonstrated that B7-H4 was an independent predictor for advanced tumor stage. The monoclonal antibody of B7-H4 has the potential anti-proliferative effects on inhibiting the chemoresistant TNBC cell lines and increasing the sensitivity of TNBC cell lines to doxorubicin, paclitaxel or carboplatin. RNAi-mediated silencing of B7-H4 in TNBC cells enhanced drug-induced apoptosis via inhibiting PTEN/PI3K/AKT pathway, whereas reexpression of B7-H4 in B7-H4 knockdown and low B7-H4 expressing cells increased the phosphorylation of PI3K and AKT along with restoration of PETN expression.

Conclusions

Our data show that B7-H4 is a biomarker indicative of a poor prognosis in TNBC patients and at least partially downregulated in chemoresistance via PTEN/PI3K/AKT pathway. Targeting B7-H4 might provide an attractive therapeutic approach specifically for TNBC patients.
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Metadata
Title
B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer
Authors
Ling Wang
Chao Yang
Xin-bo Liu
Li Wang
Fu-biao Kang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-018-0597-9

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